Nicotine replacement continues to be the most promising treatment to date for tobacco addiction. Many questions remain, however, concerning how to optimize the effectiveness of nicotine replacement therapies. A major issue is how to prevent relapse to smoking after a quit-smoking attempt. Relapse rates are disappointingly high (typically 75 percent-80 percent), even for those receiving nicotine replacement treatment. We have planned a study very different from previous studies of nicotine replacement. Our study will be guided by the basic concept that generally characterizes medical management of any disorder: individualization of treatment based upon physiological characteristics unique to each person. Our plan is to test the efficacy of a procedure for tailoring the degree of nicotine replacement to match the smoker's usual nicotine intake using nicotine patches. We will randomly assign 750 smokers to one of 5 treatment conditions. 300 subjects will be given individualized treatment to replace either 50 percent or 100 percent of their pre-quit cotinine levels (cotinine is a major metabolite of nicotine that provides a stable measure of nicotine intake). A key feature of this treatment procedure involves close monitoring of cotinine levels after cessation and subsequent adjustment of dose if necessary. An additional 300 smokers will be given fixed standard or higher-dose patches rather than tailored nicotine replacement. These smokers will provide a dose-response control condition, which will allow us to compare individualization of treatment with a simpler model involving just standard or higher-dose patches. A final control group of 150 subjects will be given only placebo patches, to allow comparisons with a no-treatment condition. Our central hypothesis is that those who receive tailored 100 percent replacement (i.e., matching their usual smoking nicotine intake with nicotine patches) will be the most likely to succeed in quitting. We will also measure relevant biological, behavioral, and withdrawal variables. These data will allow us to examine mechanisms by which greater nicotine replacement affects cessation rates, to study effects of greater nicotine replacement for important subgroups of smokers (e.g., women, depressed smokers, older smokers), and to investigate additional factors, besides degree of nicotine replacement, that may be related to abstinence or relapse. Results will provide a clear, definitive test of the hypothesis that matching the degree of nicotine replacement to usual nicotine intake improves cessation rates. If this hypothesis is supported, our findings will have major implications for the treatment of addicted smokers.